Circadian disruption induces slow-to-recover cognitive impairment and hippocampal myelin loss: a study in human beings and mice

May 2, 2026Neurobiology of disease

Disrupting the body clock causes lasting thinking problems and loss of brain insulation in humans and mice

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Abstract

Shift workers showed a maximum decrease of 14.81% in fluid intelligence scores compared to non-shift workers.

Cognitive impairment in shift workers persisted even after they stopped shift work, with a maximum reduction of 7.73% in fluid intelligence scores.
Alterations in whole-brain structural connectivity were observed in shift workers, with about 90% of structural connectivity in the bilateral hippocampi decreasing.
Mouse models demonstrated that chronic circadian disruption led to cognitive impairment and myelin loss in the hippocampus.
Following an 8-week restoration of circadian rhythms, mice continued to show inferior cognitive function associated with the hippocampus.
Recovery of myelin structure in the hippocampus was slow after circadian rhythm restoration.

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Circadian disruption, a common consequence of shift work, is associated with neuropsychiatric disorders and cognitive impairment. However, existing occupational studies lack generalizability and the underlying structural mechanisms remain unclear. The present study aimed to investigate the relationships between circadian disruption, cognitive impairment and hippocampal white matter integrity, as well as their changes following circadian rhythm restoration. We analyzed UK Biobank longitudinal cohort data, comparing cognitive performance (including reaction time, numeric memory, fluid intelligence, and prospective memory) and structural connectivity derived from diffusion magnetic resonance imaging (MRI) between shift and non-shift workers. Mouse models of chronic circadian disruption and recovery were established to complement the human findings. Compared with non-shift workers, shift workers exhibited cognitive impairment, with a maximum decrease of 14.81% in fluid intelligence scores; notably, their cognitive performance remained lower than that of never-shift workers even after ceasing shift work, with a maximum reduction of 7.73% in fluid intelligence. Higher Criticism analysis indicated alterations in whole-brain structural connectivity in shift workers, including the hippocampus, with approximately 90% of structural connectivity in the bilateral hippocampi showing a decrease (Cohen's d < 0). Murine models of 8-week circadian disruption confirmed cognitive impairment and myelin loss; furthermore, mice with 8 weeks of circadian rhythm restoration following chronic circadian disruption also displayed hippocampus-related cognitive function inferior to that of controls, as well as slow-to-recover myelin structure. This study indicates that circadian disruption induces slow-to-recover cognitive impairment; this impairment is hippocampus-associated, and the myelin architecture of the hippocampus also exhibits a slow-to-recover pattern.

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Circadian disruption induces slow-to-recover cognitive impairment and hippocampal myelin loss: a study in human beings and mice

Abstract

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